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Epstein-Barr virus (EBV) is an oncogenic herpesvirus with a worldwide seroprevalence of >90%. Like all members of the herpesvirus family, EBV establishes infection that persists for the lifetime of the host. In most healthy patients, both primary EBV infection and lifelong latent infection are benign. However, in an immunocompromised host, such as a transplant recipient, either primary infection or reactivation of latent infection can lead to severe disease. The most significant EBV-associated illness that occurs following solid-organ or hematopoietic stem cell transplantation is posttransplant lymphoproliferative disease (PTLD). In this chapter, we provide an overview of the virus, its life cycle, host immune control, diagnostic testing, and efforts at vaccine development. Particular focus is given to the clinical features, diagnosis, and management of EBV-associated PTLD.